QRM Tools / QbD

QA/QC Labs and Smart Infrastructure Equal End-to-End Quality by Design

There’s far more to becoming a paperless lab than simply eschewing paper.

By Trish Meek, Director of Product Strategy, Thermo Fisher Scientific

In his report, “Product Innovation Requires Laboratory Informatics Systems to Transcend Phases,”¹ Gartner analyst Michael Shanler recommends that manufacturers “prioritize end-to-end informatics investments and align metrics for innovation, domain expertise, operational efficiencies and quality.” His recommendation is based on an observation that today’s laboratories “are, for the most part, disconnected.”

The move to a more connected laboratory is driven by both the productivity drivers Gartner describes and significant technology improvements. The paperless lab has been discussed for the past 15–20 years, but it is finally happening and nowhere is this more evident than inside quality assurance/quality control (QA/QC) laboratories. Few QA/QC labs still cling to the paper-based notebook systems of the past and, while this is a critical step, it is only part of the story. There’s far more to becoming a paperless lab than simply eschewing paper. Labs must adopt a smart infrastructure that drives quality, not only in the lab, but throughout the organization. An integrated informatics solution is the engine that drives quality product release and a culture of continual process improvement.

In 2004, the FDA introduced Quality by Design (QbD) in “Pharmaceutical cGMPs for the 21st Century—A Risk-Based Approach.”² While this concept is not new to many industries, it was the first attempt to apply these principles to the pharmaceutical industry. Quality by Design is built on the concept that well-understood products and processes are more efficient and produce higher-quality products resulting in less product nonconformance. The FDA’s goal was to improve pharmaceutical companies’ productivity, ensure patient safety, and prevent drug shortages in the marketplace. The quote below, from a 2012 FDA presentation on the pharmaceutical quality system, makes this point succinctly:

      We rely upon the manufacturing controls and standards to ensure that time and time again, lot
      after lot, year after year the same clinical profile will be delivered because the product will be    
      the same in its quality…. We have to think of the primary customers as people consuming that
      medicine and we have to think of the statute and what we are guaranteeing in there, that the  
      drug will continue to be safe and effective and perform as described in the label.
      (Janet Woodcock, M.D.)

Uncompromising quality is essential to any pharmaceutical company. Informatics plays a critical role in ensuring that organizations realize the improved product quality and operational efficiency provided by adherence to QbD principles.

QA/QC laboratories need a tightly controlled process and a well-managed laboratory to drive predictive analytics and to prevent substandard products before they occur. An end-to-end informatics solution warns the organization before nonconformances occur by monitoring critical product attributes creating a proactive versus reactive environment. Laboratories address these needs through the use of several systems: Lab Execution Systems (LES), Scientific Data Management Systems (SDMS), and Laboratory Information Management Systems (LIMS).

LES has become a critical component of today’s paperless lab, ensuring that quality processes are followed in the laboratory and that the methods built on QbD principles are followed in day-to-day laboratory operations. LES drives users through any laboratory procedure in a stepwise fashion. This provides technicians with the direction they need to execute processes safely, and in a consistent manner. It also assures laboratory management that good laboratory practices (GLPs) are used and that standard operating procedures (SOPs) are being followed by experienced and newly trained laboratory personnel. Maintaining a consistent approach to activities like sample preparation, instrument calibration, maintenance, and analytical testing is critical to a good scientific process. Lab managers can then be certain that all of their results are a true assessment of final product quality.

An SDMS lets you integrate instruments across the lab and centralize data capture, allowing for long-term data archiving and, more importantly, data visualization from the archive—all accessed from the LIMS. An SDMS archives the original raw data files from the instrument along with a normalized representation in XML, without the need to restore the data to the original instrument workstation or install the instrument software on every computer.

The real scientific data and the results gleaned from them are a critical part of QbD. The final product specification is determined by comparing the analytical results to determine which formulation and process parameters yield the best product. As part of a paperless lab environment, an SDMS integrated with the LIMS reduces paperwork, manual review time, and data transcription, which improves efficiency, productivity, consistency, and quality while reducing costs dramatically. SDMS also provides secure access to archived files for as long as necessary, and enables more efficient and defensible reporting to regulatory authorities.

LIMS remains a critical part of the infrastructure of any pharmaceutical manufacturing organization. Today’s LIMS goes far beyond just the management of samples, tests, and results. It also provides resource management, allowing organizations to forecast fewer sample volume and resource needs. It provides dashboard views that allow organizations to see how their lab is operating and identify any data that are trending toward warning or failure limits. These lab management activities are essential, but organizations need to be able to drive the day-to-day operations of the laboratory as well.

Having a smart infrastructure built on a state-of-the-art informatics solution at its core enables another critical benefit in the lab: automation. Even smart instruments must undergo regular performance verification. How often this is done depends on many factors, including the frequency of use. Because instrument failure—or having a system go out of specification— can negatively impact quality, production, or compliance down the road, any risk is unacceptable. A LIMS can save considerable time by helping labs adhere to precise rules and requirements, automating critical procedures on predefined schedules.

When all systems are aligned, the convergence of people, processes, and technology is transformative. Problems arise when these systems are not fully integrated, and these disparate systems become out of sync. At a macro level, breakdowns occur at three key points: data capture, data transcription, and data management. Put another way, the key to an efficient lab that delivers uncompromising quality is having smart instruments within a smart infrastructure. This starts with SOPs for highly standardized methods and processes, which are handled by the LES, and includes raw instrument data generated by the analytical instruments used in those experiments, all of which are handled capably by the SDMS.

What lab managers really want is a truly connected system that provides lab management, drives lab operations, and integrates all of the data-generating sources and ties all the data together in one centralized location. A modern LIMS needs to be a complete informatics infrastructure by providing a LIMS, SDMS, and LES in one.

Today’s paperless lab can more aptly be called an integrated lab. The trinity of LIMS/LES/SDMS enables lab managers to achieve full instrument integration, manage their methods and workflows, retrieve and archive any kind of raw laboratory data, and export those results across the organization to enterprise resource planning (ERP) systems, for example, all in whatever format is required by recipients.

The ability to manage the entire process in a tightly integrated solution, one that functions as a single piece of software, dramatically streamlines laboratory operations while minimizing the cost of ownership, implementation, validation, and ongoing maintenance. An example of this is SampleManager LIMS (Thermo Fisher Scientific), which includes built-in functionality for LIMS, LES, and SDMS as well as integration technologies. What’s more, when labs plan for such seamless integration it enables lab managers to codify a “do it right every time” process approach, which is in alignment with QbD processes, providing the transparency necessary to identify and remove nonvalue-add steps, while lowering the cost of training new staff. With LES functionality available as part of a LIMS implementation, SOPs and methods are automatically established electronically so that for any lab personnel, new or seasoned, the LIMS acts as their workflow, manual, and constant guide.

It is easy to see the LIMS, LES, and SDMS “stack” as a lab-centric view of pharmaceutical business, but that would be a mistake. The ability to run efficient labs and protect the brand by safeguarding product quality is an enterprise-level concern. As such, the LIMS needs to be fully integrated with ERP systems; in fact, many work requests coming into QA/QC laboratories are actually initiated in a manufacturer’s ERP system, which for many companies is the bridge between its manufacturing execution system (MES) and other systems such as the LIMS.

In many organizations, a LIMS is a standalone investment, managing workflow and sample testing and generating appropriate reports. If the lab needs additional software, such as an electronic laboratory notebook (ELN) or SDMS, those systems are then implemented and sometimes, but not always, integrated with the LIMS so that lab operations are more streamlined and data are easier to manage. In a QA/QC lab, however, a LIMS such as SampleManager, that is prebuilt with LES and SDMS functionality and delivers end-to-end workflow and data capture, is literally designed for quality. The benefits of having all these capabilities resident in a single system are myriad, starting with lower total cost of ownership, ease of training and administration, streamlined compliance, and better overall quality control. All of this is possible across vast geographies or contractual partnerships, and can all be managed holistically.

Organizations that have not done so already need to make this year a major inflection point for laboratory technology, especially within the QA/ QC function. After all, the evidence is stacking up that the costs of inaction clearly outweigh the investment that is required for change.


1. https://www.gartner.com/doc/2597215/product-innovation-requireslaboratory-informatics
2. http://www.fda.gov/ohrms/dockets/ac/03/briefing/3933B1_02_Pharmaceutical%20cGMPs.pdf

Trish Meek is Director of Product Strategy, Thermo Fisher Scientific, 1601 Cherry St., Philadelphia, PA 19102, U.S.A.; tel.: 215-964-6020; e-mail: trish.meek@thermofisher.com; http://www.thermoscientific.com/informatics




Free Subscriptions

Pharma Manufacturing Digital Edition

Access the entire print issue on-line and be notified each month via e-mail when your new issue is ready for you. Subscribe Today.

pharmamanufacturing.com E-Newsletters

A mix of feature articles and current new stories that are critical to staying up-to-date on the industry, delivered to your inbox. Choose from an assortment of different topics and frequencies. Subscribe Today.